Single vs Double strand DNA Breaks (Rad Bio 101 for Technologists) скачать в хорошем качестве

Single vs Double strand DNA Breaks (Rad Bio 101 for Technologists)

Single vs Double strand DNA Breaks describe two types of DNA damage where single strand breaks are more common, but double strand breaks are much more damaging. These are some of the basics of Radiation Biology 101 along with x-rays depositing energy locally as electrons, and then electrons ionizing surrounding molecules to generate free radicals that are chemically unstable. For more detailed information see our post: https://howradiologyworks.com/radiati... An average human body with weight of 80 kg has DNA which is not more than 20 grams, or DNA is only 0.25% percent of the whole human body. When x-rays interact with the body, they deposit energetic electrons. These electrons can cause direct or indirect damage to the DNA. DNA has four pairs on a sugar backbone, and these same base pairs make up a double helix. The base pairs are adenine, thymine, cytosine, and guanine, called A, T, C, and G. We know that the A and T are always paired together, and the C and G are always paired together as well. Single strand breaks can be repaired fairly easily using the other strand as a template. So if there was an A-T pairing and the A was destroyed it is clear that since there is a T present that the A should be replaced in the missing strand. Chapters: 00:00. Intro DNA 01:10 X-rays photoelectric, Compton 02:45. Direct vs indirect DNA damage 04:12. Single vs Double strand DNA breaks 05:48. Summary X-rays - electrons - DNA damage (directly or via Free Radicals) However, if there is a double strand break this is more difficult to repair as not a template to use in the repair. Therefore, double strand breaks are more problematic. During replication if there is sufficient damage to the DNA this can lead to a global response for enzyme repair mechanisms that are at the chromosomal level, not just the base pair level (chemical repair). And if these mechanisms fail a global response of apoptosis or programmed cell death can be triggered, in order to preserve the larger organism. Here we focus on the local damage from the x-rays with matter. As we discussed in that post both Compton and Photoelectric effect result in energetic (i.e. fast) electrons being generated locally in the body. These electrons deposit their energy locally so they do not affect the image signal generated in x-ray imaging, but they do lead to tissue damage. When x-ray photons interact with the body, they excite atoms. If energy of photon isn’t enough to free an electron, dissipation of heat occurs. Both Compton and Photoelectric Effects lead to the generation of energetic electrons. Direct Damage (Energetic Electrons) These energetic electrons can interact with DNA that is within a few nanometers (10-9m). This is referred to as direct action since it is the energetic electrons that are directly causing the damage to the DNA. Indirect Damage (Free Radicals) There is an alternative pathway for DNA damage where the electrons cause the DNA damage indirectly. These charged ions then undergo a chemical reaction with other molecules to generate Free Radicals. These Free Radicals while not charged are chemically unstable. Free radicals that remain within a few nanometers away from the DNA can damage the DNA. We refer to this as indirect action since it was not the electrons directly causing the damage, but rather the energetic electrons generate chemically unstable molecules (Free Radicals) which cause this DNA damage. Indirect action is responsible for more of the DNA damage than direct action. In some instances the DNA damage can be repaired. In this case long term damage can be avoided. However, if there is damage that cannot be repaired, this can lead to DNA mutations or cell death. In the case of cell death, the resulting outcome will be dependent on the radiation dose and the tissue being irradiated. Possible consequences of cell death at large scale include– acute radiation sickness and fetal developmental effects. If it’s an embryo/fetus that is receiving the radiation there are specific concerns which a very dependent on the stage of gestational development. The other option that can happen and has longer-term consequences is DNA mutation. DNA mutations can cause cancer (Radiation Carcinogenesis ) in a process that takes many years. As we discussed above in the biological background section single strand breaks can be more easily repaired than double strand breaks. In terms of the damage from x-rays this can be caused by both direct interaction with the electrons or by indirect interaction via free radicals which can cause damage to the DNA. If the electron damages to the DNA directly, it’s what’s called direct damage. Alternatively, indirect damage is when the energetic electrons generate Free Radicals that then do the damage. About two-thirds of the damage is caused by the free radicals. And if the damage occurs in a double strand break, it’s much more damaging because it’s much more difficult to repair.